Our laboratory has been studying the molecular mechanism of liver fibrosis. We seek to understand how chronic liver injury and hepatocyte cell death trigger the activation of hepatic stellate cells, the main fibrogenic cells of the liver, leading to the deposition of extracellular matrix. We have shown that the activation of NADPH oxidases by the efferocytosis of apoptotic cells plays an essential role in stellate cell activation. Based on these findings, we have extended our studies to explore the specific role of NADPH oxidases in nonalcoholic steatohepatitis (NASH). NASH is becoming one of the most common liver diseases, with diabetes as a major risk factor for developing progressive steatohepatitis and fibrosis. Our goal is to delineate the cell-specific roles of the NADPH oxidase homologs and to dissect the redox-mediated molecular pathways creating a proinflammatory and fibrogenic milieu in the liver. Completion of these studies will facilitate the development of novel treatment strategies and translational trials targeting NADPH oxidases in diabetes and NASH.
Natalie J. Torok, MD